Table Of Content

National Institutes of Health National Institute of General Medical Sciences The Chemistry of Health U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service NIH Publication No. 00-4121 National Institutes of Health September 2000 National Institute of General Medical Sciences www.nigms.nih.gov Contents FOREWORD IV THE PATHWAYS OF LIFE VI CHAPTER 1: ACTIONS AND REACTIONS 2 It’s a Gas! 4 Chemical Biology in Action: Just Say NO 5 Chemical Biology in Action: Folic Acid Saves the Day 6 Building Blocks 8 From Mice to...Bacteria? 10 Chef}iical Biology in Action: Chemistry to the Rescue 11 Question Box: Computer Labs 12 CHAPTER 2: HARNESSING BIOLOGY’S MAGIC 14 It’s Biology, It’s Chemistry.. .It’s Engineering! 14 Endless Possibilities 16 Chemistry for a Greener World 17 Tiny Bits of Help 18 Metals Can Be Good for You... 19 .. .or Metals Can Be Bad for You 20 Metals in Health and Disease 20 Question Box: Future Factories 21 CHAPTER 3: SUGARS AND FATS: ARE WE WHAT WE EAT? 22 Form and Function 23 Fats That Protect Bacteria Can Harm People 25 Sugar-Coated Proteins 26 Chemical Biology in Action: Sticky Situations 27 A Complicated Recipe 28 One-Pot Synthesis 31 Question Box: Putting Things in Order 32 CHAPTER 4: A CHEMIST'S TOOLBOX 34 A Model Cell 35 This Is Organic Chemistry? 36 A Room Without Much View 38 Pass the Chip, Please 39 The Many Faces of DNA 41 Question Box: Life on the Edge 44 CHAPTER 5: THE HEALING POWER OF CHEMISTRY 46 Looking to Sea 47 Making Medicines 50 Chemical Biology in Action: Library Research Pays Off 51 Getting It Left or Getting It Right? 52 Losing Medicines 55 Chemical Biology in Action: The Shape of Things to Come 56 Making Good Medicines Better 57 Question Box: Tools for New Medicines 58 CHEMISTRY FOR THE FUTURE 60 GLOSSARY 61 Foreword How could anybody fit all of chemistry into Chemistry is anything but stale or static. Countless numbers of chemical reactions work ceaselessly 60 pages? You're skeptical that such a feat inside your body, allowing you to think, breathe, and eat. Chapter 1, “Actions and Reactions,” aims could possibly be accomplished, and with to convey the essential and wondrous notion that good reason. The Chemistry of Health cannot the chemistry inside your body never stops. Cascades of repeating biochemical relays keep your pretend to cover such an enormous area of organ systems operating smoothly and efficiently. Your body’s metabolic factories break down the science in so few pages. We wouldn't even food you eat and recycle the components back into want to try. Instead, this science education basic building blocks from which your tissues and organs are built. booklet aims to offer a sampling of how Scientists hunger for information since, like everybody else, they are curious people. But a key basic chemistry and biochemistry research reason biological scientists strive to learn how can spur a better understanding of human living systems work is so they can redesign the broken metabolic circuits that contribute to many health. We also want you to witness the diseases. Chemists, like most biologists, want to learn how best to employ primitive organisms fascination of research alive in today's like bacteria and yeast, not only to probe funda¬ chemistry labs. mental biological questions but also to produce the valuable commodities we call medicines. Chapter 2, “Harnessing Biology’s Magic,” explores how bio¬ technology offers rich potential toward bettering human health. Perhaps one of the most amazing triumphs of the human body is the fact that all you really need to do to keep your body running is to eat and to sleep. The rest seems to take care of itself. Of course, much sophisticated biochemistry goes on behind the scenes, as your body efficiently churns out energy from the sugars, fats, and pro¬ teins you eat every day. Chapter 3, “Sugars and Fats: Are We What We Eat?” describes how carbo¬ drugs to treat diseases. Scientists take careful note hydrates and lipids (the scientific names for sugars of the chemical warfare waged among creatures and fats) provide much of the structural scaffolding of the land and sea. For example, molecules for cells, organs, and tissues. This chapter also produced by microbes for defense against other highlights a new frontier in chemistry research— organisms their own size can point the way how the sugars that adorn the surface of cells affect toward developing powerful antibiotic drugs to the way cells move about in the body. This knowl¬ treat infections in people. edge holds great promise in helping researchers Much of the science described in the pages devise ways to prevent diseases such as cancer that follow has been funded through U.S. tax and conditions such as inflammation that rely on dollars invested in biomedical research projects at cell movement. universities. The National Institute of General As technology advances at a swift pace, Medical Sciences (NIGMS), which funded most of researchers’ tools evolve to be ever smaller and these research projects, is unique among the com¬ more efficient. The first computers ever made ponents of the National Institutes of Health (NIH) were so huge they nearly filled a room. Today, most in that its main goal is to promote basic biomedical people’s personal computers fit snugly into a desk research that at first may not be linked to any par¬ corner. Some of the computers of tomorrow may ticular body part or disease. In time, however, these fit into the palm of your hand, or even perhaps scientific studies on the most fundamental of life’s be too small to see! Chemists are masters of mate¬ processes—what goes on inside and between rials, and an increasing number are looking to cells—can shed brilliant light on important health Nature’s toolbox to create tiny biological probes issues, including what causes certain diseases and and instruments. Scientists can now eavesdrop how to treat them safely and effectively. on the movements of single molecules and create miniature devices such as robots and computers, Alison Davis, Ph.D. using traditionally “biological” ingredients like the Science Writer, NIGMS building blocks of DNA. Chapter 4, “A Chemist’s September 2000 Toolbox,” offers a glimpse into the technological wonder propelling the chemistry of today and tomorrow. And finally. Chapter 5, “The Healing Power of Chemistry,” visits some unusual places that may yield future medicines. Medicinal chemists search far and wide for molecules that could be useful The Pathways of Life Dear “Ask the Doctor”: Like Confused, many of us have an encounter After a recent annual physical exam, my doctor’s with biochemistry without even knowing it. office informed me that I have “elevated liver In health and in disease, our bodies are bio¬ enzymes.” Now she says 1 need to come back chemical laboratories abuzz with activity, where for further tests. What does all this mean, and molecules are constantly being made, used, broken am I in danger?” down, and recycled. What does the lion’s share of Confused the work? Indispensable molecules called enzymes. Anytown, USA When routine blood tests reveal abnormally high liver enzyme levels, for instance, there are Is Confused in danger? Could be; but most many potential causes, depending on which likely not. To get to the bottom of questions like enzyme levels are awry and how off-kilter the this, doctors ask patients a lot of questions. levels are. The culprit could be as serious as “How do you feel?” alcoholism or infection with one of the hepatitis “Have you eaten anything unusual lately?” viruses, both of which can cripple the liver over “On any new medications?” time. Or the cause could be as innocuous as taking And often, doctors will perform more tests, certain common medicines or having a few extra prompting the patient’s body to yield a bint as drinks at a party. to what’s wrong—some due as to why a most Many of the body’s enzymes reside inside cells. carefully maintained balance of natural chemicals If cells are damaged, they break apart and spill their has gone askew. contents into neighboring body fluids, like blood. The presence of higher-than-normal levels of enzymes in the blood can signify trouble in the tissues or organs (such as the liver) that those cells normally populate. But sometimes, abnormal lab results mean nothing at all. Elevated enzyme levels caused by the body’s processing of “toxins”—including substances like chemicals in the environment, prescribed medicines, or alcohol—usually return to normal once the foreign substance is gone from the scene. The liver is not the only place enzymes hang out. Every cell in every organ—from the liver to the heart to the skin—is chock full of enzymes. Foreword I vii Anything but innocent bystanders, enzymes are the reason why cells are bustling centers of activity. Enzymes underlie our ability to move, to think, to sense our world. Enzymes help us wink an eye, savor an ice cream cone, and catch a sticky drip about to fall off the edge of the cone. Enzymes, and their essential cellular associates—other proteins, nucleotides, sugars, and fats—allow a stubbed toe to heal properly and nurture a fetus growing inside a woman’s body. But when they are not working properly, enzymes can cause disease. Cancer can happen when the enzymes that copy the genetic material DNA make mistakes, giving rise to an errant gene that produces a faulty protein, or no protein at all. In Control If that particular protein is the one that keeps a given set of cells from multiplying out of control, It seems to happen the only knows for sure relationship at all— same way every time: that A causes B if he just by coincidence then its absence can bring about dire consequences. You go to the doctor or she knows that dur¬ you happen to get Although a scientist may study a couple of for a check-up, and a ing the experiment, the the sniffles around the couple of days later, presence of A was time you go for your isolated enzymes in the laboratory, inside the you end up with a necessary for effect B yearly check-up. Is it body enzymes are never lonely. They link up to cold. Your conclusion: to happen. That is—A always in the spring Sitting in the doctor's doesn't also cause C, when pollen counts form vibrant networks and pathways. The study of waiting room made D, E, and F. Or, that B are rising? Scientists biochemical pathways and networks, and how they you sick. Believe it didn't happen on its must carefully design or not, this everyday own, without any input experiments so that reverberate and influence each other, is the science situation resembles from A. In the waiting they can account for of life and the chemistry of health. scenarios scientists room example, for the influences of as face all the time in instance, it could be many variables as they their labs. A scientist's that going to the doc¬ can think of. Usually, perpetual challenge tor truly does make researchers do this is to evaluate cause you prone to getting by comparing the test and effect, and then sick, because in the group with a control, make conclusions. waiting room, you or untreated, group. Key to this process is are exposed to more Only then do their researchers' use of germs than usual. But experiments really "controls." A scientist perhaps there's no "work." CHAPTER 1 Actions and Reactions E ven though you’re probably sitting down starting materials (called substrates) and convert¬ while you’re reading this, your body is any¬ ing them into finished materials (called reaction thing but static. Thousands of enzymes in your products). One secret to an enzyme’s success in body toil away every second of every day, breaking this endeavor is its shape. An enzyme is shaped so apart the components of the foods you eat into that it can hug its substrate tightly. This molecular energy for essential life processes. Vision, move¬ embrace triggers chemical changes, shuffling ment, memory—you name it, there are enzymes chemical attractive forces called “bonds” and pro¬ at work behind the scenes. ducing new molecules. Only enzymes that have an Enzymes work by making it possible for chemi¬ exact fit with their substrates do a decent job of cal reactions inside your body to take place. While speeding up chemical reactions. But things don’t that might not seem significant, consider end there; reactions are not singular events. They the fact that without the help of enzymes, the re-occur, over and over again. Enzymes are the key conversion of nutrients and minerals into usable players linking up chain reactions of the chemical biological molecules such as proteins and nucleic events that culminate in our everyday physiology. acids might take weeks, even years. Enzymes can Much like a cascade of dominoes, the product of make this happen in minutes, sometimes seconds. one chemical reaction becomes the substrate for How do they do it all, and so well? Enzymes act another. Enzymes form the core of these ordered like the accelerator pedal of a car. But they also pathways, which themselves are the basis for play the role of matchmaker, bringing together metabolism. In a grand sense, metabolism is the What Is Biochemistry? Simply stated, tioning unit using biochemistry is life. molecular tools called Practically stated, enzymes. Creatures biochemistry is our life: as distinct as bacteria, what we are and how giraffes, and people we live. Our bodies are use many of the same very busy factories, biochemical toolsets extracting energy from to survive, eat, move, the foods we eat, build¬ and interact with their bi*o*chem*is*try (bi'o kem'is tree): ing cells and tissues, respective environ¬ and knitting everything ments. Biochemistry n., the chemistry of living organisms. together into a func¬ underlies our health.